Proliferative vitreoretinopathy (PVR) is a blinding fibrotic eye disease that develops in 8-10% of patients who undergo primary retinal detachment-reparative surgery and in 40-60% of patients with open-globe injury. At present, there is no pharmacological treatment for this devastating disease. Vitreal growth factors activate their respective receptors of cells in the vitreous, trigger their downstream signaling transduction (e.g. phosphoinositide 3 kinases (PI3Ks)/Akt), and drive cellular responses intrinsic to the pathogenesis of PVR. PI3Ks play a central role in experimental PVR. However, which isoform(s) are involved in PVR pathogenesis remain unknown. Herein, we show that p110δ, a catalytic subunit of receptor-regulated PI3K isoform δ, is highly expressed in epiretinal membranes from patients with PVR, and that idelalisib, a specific inhibitor of PI3Kδ, effectively inhibits vitreous-induced Akt activation, proliferation, migration and contraction of retinal pigment epithelial cells derived from an epiretinal membrane of a PVR patient. Small molecules of kinase inhibitors have shown great promise as a class of therapeutics for a variety of human diseases. The data herein suggest that idelalisib is a promising PVR prophylactic.

中文翻译：

---

依达拉西布抑制玻璃体诱导的Akt活化和来自视网膜前膜的视网膜色素上皮细胞的增殖。

增生性玻璃体视网膜病变（PVR）是一种致盲性纤维化眼病，在接受原发性视网膜脱离修复手术的8-10％的患者和40-60％的全球性眼球损伤的患者中发展。目前，尚无用于治疗这种破坏性疾病的药物。玻璃体生长因子激活玻璃体中各自的细胞受体，触发其下游信号转导（例如磷酸肌醇3激酶（PI3Ks）/ Akt），并驱动PVR发病机制固有的细胞应答。PI3K在实验性PVR中起着核心作用。然而，PVR发病机制中涉及哪些同种型仍然未知。在这里，我们显示p110δ是受体调节的PI3K亚型δ的催化亚基，在PVR患者的视网膜前膜中高度表达，而艾达利西布，PI3Kδ的一种特异性抑制剂可有效抑制玻璃体诱导的Akt活化，增殖，迁移和收缩，该视网膜色素上皮细胞源自PVR患者的视网膜前膜。激酶抑制剂的小分子作为治疗多种人类疾病的一类疗法已显示出巨大的希望。本文中的数据表明艾达拉西布是有前途的PVR预防剂。